Multi-valued solutions and branch point singularities for nonlinear hyperbolic or elliptic systems

Multi-valued solutions are constructed for 2 × 2 first-order systems using a generalization of the hodograph transformation. The solution is found as a complex analytic function on a complex Riemann surface for which the branch points move as part of the solution. The branch point singularities are envelopes for the characteristics and thus move at the characteristic speeds. We perform an analysis of stability of these singularities with respect to perturbations of the initial data. The generic singularity types are folds, cusps, and nondegenerate umbilic points with non-zero 3-jet. An isolated singularity is generically a square root branch point corresponding to a fold. Two types of collisions between singularities are generic: At a “tangential” collision between two singularities moving at the same characteristic speed, a cube root branch point is formed, corresponding to a cusp. A “non-tangential” collision, between two square root branch points moving at different characteristic speeds, remains a square root branch point at the collision and corresponds to a nondegenerate umbilic point. These results are also valid for a diagonalizable n-th order system for which there are exactly two speeds. © 1993 John Wiley & Sons, Inc.     

Computational combinatorial ligand design: Application to human α-thrombin

Summary A new method is presented for computer-aided ligand design by combinatorial selection of fragments that bind favorably to a macromolecular target of known three-dimensional structure. Firstly, the multiple-copy simultaneous-search procedure (MCSS) is used to exhaustively search for optimal positions and orientations of functional groups on the surface of the macromolecule (enzyme or receptor fragment). The MCSS minima are then sorted according to an approximated binding free energy, whose solvation component is expressed as a sum of separate electrostatic and nonpolar contributions. The electrostatic solvation energy is calculated by the numerical solution of the linearized Poisson-Boltzmann equation, while the nonpolar contribution to the binding free energy is assumed to be proportional to the loss in solvent-accessible surface area. The program developed for computational combinatorial ligand design (CCLD) allows the fast and automatic generation of a multitude of highly diverse compounds, by connecting in a combinatorial fashion the functional groups in their minimized positions. The fragments are linked as two atoms may be either fused, or connected by a covalent bond or a small linker unit. To avoid the combinatorial explosion problem, pruning of the growing ligand is performed according to the average value of the approximated binding free energy of its fragments. The method is illustrated here by constructing candidate ligands for the active site of human -thrombin. The MCSS minima with favorable binding free energy reproduce the interaction patterns of known inhibitors. Starting from these fragments, CCLD generates a set of compounds that are closely related to high-affinity thrombin inhibitors. In addition, putative ligands with novel binding motifs are suggested. Probable implications of the MCSS-CCLD approach for the evolving scenario of drug discovery are discussed.     

A sphere-based model for the electrostatics of globular proteins

We propose a model for the electrostatics of globular proteins in which the low dielectric region is replaced by concentric spheres of the appropriate size. The method uses analytical formulas for the dielectric sphere and allows an efficient and accurate treatment of bulk charges. For surface charges, we propose a numerical determination of the sphere radius based on the solvent exposure of the individual atoms. The present implementation of the sphere model yields a good approximation of finite-difference Poisson solvation and interaction energies for a test set of 12 proteins.     

Multiple domain dynamics simulated with coupled level sets

We adapt the level-set method to simulate epitaxial growth of thin films on a surface that consists of different reconstruction domains. Both the island boundaries and the boundaries of the reconstruction domains are described by different level-set functions. A formalism of coupled level-set functions that describe entirely different physical properties is introduced, where the velocity of each level-set function is determined by the value of the other level-set functions.     

Zero Viscosity Limit for Analytic Solutions of the Navier-Stokes Equation on a Half-Space.¶ II. Construction of the Navier-Stokes Solution

This is the second of two papers on the zero-viscosity limit for the incompressible Navier-Stokes equations in a half-space in either 2D or 3D. Under the assumption of analytic initial data, we construct solutions of Navier-Stokes for a short time which is independent of the viscosity. The Navier-Stokes solution is constructed through a composite asymptotic expansion involving the solutions of the Euler and Prandtl equations, which were constructed in the first paper, plus an error term. This shows that the Navier-Stokes solution goes to an Euler solution outside a boundary layer and to a solution of the Prandtl equations within the boundary layer. The error term is written as a sum of first order Euler and Prandtl corrections plus a further error term. The equation for the error term is weakly nonlinear; its linear part is the time dependent Stokes equation. This error equation is solved by inversion of the Stokes equation, through expressing the solution as a regular (Euler-like) part plus a boundary layer (Prandtl-like) part. The main technical tool in this analysis is the Abstract Cauchy-Kowalewski Theorem. Received: 5 September 1996 / Accepted: 14 July 1997     

Zero Viscosity Limit for Analytic Solutions, of the Navier-Stokes Equation on a Half-Space.¶I. Existence for Euler and Prandtl Equations

This is the first of two papers on the zero-viscosity limit for the incompressible Navier-Stokes equations in a half-space. In this paper we prove short time existence theorems for the Euler and Prandtl equations with analytic initial data in either two or three spatial dimensions. The main technical tool in this analysis is the abstract Cauchy-Kowalewski theorem. For the Euler equations, the projection method is used in the primitive variables, to which the Cauchy-Kowalewski theorem is directly applicable. For the Prandtl equations, Cauchy-Kowalewski is applicable once the diffusion operator in the vertical direction is inverted. Received: 5 September 1995 / Accepted: 14 July 1997     

The fluid dynamic limit of the nonlinear boltzmann equation

Solutions of the nonlinear Boltzmann equation are constructed up to the first appearance of shocks in the corresponding fluid dynamics. This construction assumes the knowledge of solutions of the Euler equations for compressible gas flow. The Boltzmann solution is found as a truncated Hilbert expansion with a remainder, and the remainder term solves a weakly nonlinear equation which is solved by iteration. The solutions found have special initial values. They should serve as “outer expansions” to which initial layers, boundary layers and shock layers can be matched.